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1.	Nichols, E, et al. (author) Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019 2022 In: The Lancet. Public health. - 2468-2667. ; 7:2, s. E105-E125 Journal article (peer-reviewed)
2.	Kvedaraite, E, et al. (author) Notch-dependent cooperativity between myeloid lineages promotes Langerhans cell histiocytosis pathology 2022 In: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 7:78, s. eadd3330- Journal article (peer-reviewed)abstract Langerhans cell histiocytosis (LCH) is a potentially fatal neoplasm characterized by the aberrant differentiation of mononuclear phagocytes, driven by mitogen-activated protein kinase (MAPK) pathway activation. LCH cells may trigger destructive pathology yet remain in a precarious state finely balanced between apoptosis and survival, supported by a unique inflammatory milieu. The interactions that maintain this state are not well known and may offer targets for intervention. Here, we used single-cell RNA-seq and protein analysis to dissect LCH lesions, assessing LCH cell heterogeneity and comparing LCH cells with normal mononuclear phagocytes within lesions. We found LCH discriminatory signatures pointing to senescence and escape from tumor immune surveillance. We also uncovered two major lineages of LCH with DC2- and DC3/monocyte-like phenotypes and validated them in multiple pathological tissue sites by high-content imaging. Receptor-ligand analyses and lineage tracing in vitro revealed Notch-dependent cooperativity between DC2 and DC3/monocyte lineages during expression of the pathognomonic LCH program. Our results present a convergent dual origin model of LCH with MAPK pathway activation occurring before fate commitment to DC2 and DC3/monocyte lineages and Notch-dependent cooperativity between lineages driving the development of LCH cells.

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Type of publication: journal article (2)

Type of content: peer-reviewed (2)

Author/Editor: Jain, V. (1); Gupta, R. (1); Brayne, C (1); Hussain, R. (1); Rezaei, N (1); Abd-Allah, F (1); show more...; Abualhasan, A (1); Abu-Gharbieh, E (1); Alahdab, F (1); Alanezi, FM (1); Alipour, V (1); Ansari, I (1); Arabloo, J (1); Ayano, G (1); Baig, AA (1); Baune, BT (1); Bejot, Y (1); Bhagavathula, AS (1); Bhattacharyya, K (1); Bijani, A (1); Bolla, SR (1); Boloor, A (1); Brenner, H (1); Burkart, K (1); Camera, LA (1); Carvalho, F (1); Catala-Lopez, F (1); Cerin, E (1); Chalek, J (1); Cherbuin, N (1); Chu, DT (1); Costa, VM (1); Dandona, L (1); Dandona, R (1); da Silva, DD (1); Diaz, D (1); Douiri, A (1); Edvardsson, D (1); El Sayed, I (1); Eskandari, K (1); Eskandarieh, S (1); Esmaeilnejad, S (1); Faro, A (1); Feigin, VL (1); Fereshtehnejad, SM (1); Fernandes, E (1); Ferrara, P (1); Filip, I (1); Fischer, F (1); Fukutaki, K (1); show less...

University: Karolinska Institutet (2)

Language: English (2)

Year: 2022 (2)Undo refine

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